Social stress induces bone loss and growth plate reduction

/Abstract Psychological stress is an established contributor to bone and tooth loss and impaired bone growth. In the US, more than 50 million people currently experience bone loss while a similar number is afflicted by anxiety (40 million) and/or depressive disorders (16 million). Bone and tooth loss resulting from psychological stress has been observed in all age populations. A murine model of stress, repeated social defeat (RSD), recapitulates key physiological, immunological, and behavioral alterations in humans exposed to psychosocial stress such as bullying and loss of social status. RSD activates the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system to create a state in which primed, pro-inflammatory monocytes traffic from the bone marrow to the brain to generate neuroinflammation and anxiety-like behavior. In addition, RSD rapidly induces bone loss through increased activity of osteoclasts, and bone growth plate reduction. However, the precise mechanisms by which RSD influences bone have not been identified. Therefore, the overall goal of this project is to exploit a rodent model of psychological stress to better explore the relationships between immunological processes, mental and bone health. This will be accomplished in three Specific Aims. Aim 1 will examine the kinetics of bone loss and growth plate reduction in adolescent male and female mice following a period of RSD. Aim 2 will investigate a central role for osteoclast activation and chemokine (CXCL12) signaling in RSD-induced monocyte mobilization. Aim 3 will investigate mechanisms of RSD-induced growth plate reduction. Outcomes of this project will help achieve the long-term goal of developing more specific interventions to treat psychological stress-related disorders of skeletal physiology. Project Number: 1R56DE034688-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Dental and Craniofacial Research (NIDCR) | Principal Investigator: Do-Gyoon Kim (+2 co-PIs) | Institution: OHIO STATE UNIVERSITY, Columbus, OH | Award Amount: $393,750 | Activity Code: R56 | Study Section: Skeletal Biology Development and Disease Study Section[SBDD] View on NIH RePORTER: https://reporter.nih.gov/project-details/11512402